Masses of the pituitary gland (sellar masses) are common, representing approximately 15% of all intracranial masses. About half of the sellar masses are caused by a hormone-secreting adenoma and more easily diagnosed because of classical signs and symptoms. The remaining sellar masses, however, do not secrete any hormone (32% are non-functioning pituitary adenomas, and 10% are non-adenomatous lesions), and are therefore more difficult to differentiate. Often their diagnosis is established only after transsphenoidal surgery and pathological examination. Among the group of non-functioning pituitary masses, autoimmune (lymphocytic) hypophysitis is the only disease that has an immune pathogenesis. The pituitary autoantigens targeted in hypophysitis remain unknown. If discovered, they can lead to the development of a serum test useful to distinguish hypophysitis from the other non-functioning pituitary masses. This distinction is critical for patient care: in fact, hypophysitis can be usually managed medically, whereas the other conditions typically require surgery. The proposal reports our human and mouse studies aimed to discover the pituitary autoantigens and therefore develop an antibody-based serologic test for the differential diagnosis of non-functioning pituitary masses. PUBLIC HEALTH RELEVANCE: Pituitary masses are common. Because most of them do not secrete any pituitary hormone, they can often be diagnosed only after surgery and pathological examination. Autoimmune hypophysitis is the only disease entity among the non-functioning pituitary masses that has an immune pathogenesis. This grant is designed to develop an antibody- based serologic test to aid in the differential diagnosis of these common conditions. Such test could avoid unnecessary pituitary surgeries to patients with autoimmune hypophysitis.